Several recent publications indicate that human papillomavirus (HPV) and/or HPV-related disease may play a role in acquisition of HIV infection, similar to other sexually transmitted infections (STIs). This is critically important because HPV infection may be the most common STI among Indian men who have sex with men (MSM), a group also at very high risk of HIV. If a role for HPV is confirmed, HPV vaccination may contribute to HIV prevention efforts, since effective HPV vaccines are now available. Preliminary data from a study we are now completing show that Indian HIV-seropositive MSM have a very high prevalence of anogenital HPV infection but nothing is known of the prevalence or incidence of HPV or HPV-related disease in Indian HIV- seronegative MSM. Moreover, the incidence of HIV infection is not established in this group. Our goal is to obtain critical data needed to design a definitive prospective study on the role of HPV infection in HIV acquisition. Our specific aims are: 1) To determine the one-year incidence of HIV among high-risk MSM in India;2) To test the feasibility and acceptability of recruiting a sample of 300 high-risk HIV-seronegative MSM using respondent-driven sampling (RDS) and 3) To produce preliminary descriptive data on the prevalence and incidence of HPV infection and HPV-associated disease, STIs other than HPV, sexual risk behaviors and data on other potential confounders. Men will be followed over one year at 6-month intervals for a total of 3 visits. At each visit 150 MSM at each site will be administered a questionnaire. HPV DNA samples will be collected from the anus, penis and mouth. Blood will be obtained for HIV testing. Anal cytology and high resolution anoscopy will be performed with biopsy of visible anal lesions. Penile and oral exams and biopsies will also be performed. HPV DNA testing will be performed at CMC Vellore. Training and quality assurance will be performed at the UCSF. Our results will be important for both men and women in India, since many Indian MSM have female sexual partners, and may serve as a bridge population to women. The data will be important for cancer prevention efforts in Indian MSM since HPV-related cancers may be preventable. Data on HPV will be useful for development of optimal next-generation vaccines. This study builds upon a growing collaboration between UCSF, CMC Vellore, Humsafar Trust and the AIDS Malignancy Consortium. It will lead to capacity-building and additional studies of HPV-associated diseases in India. PUBLIC HEALTH RELEVANCE: Several recent publications indicate that human papillomavirus (HPV) and/or HPV-related disease may play a role in acquisition of HIV infection, similar to other sexually transmitted infections (STIs). If confirmed, HPV vaccination may play a role in HIV prevention efforts, since effective HPV vaccines are now available. Our goal is to obtain critical preliminary data needed to design a definitive prospective study on the role of HPV infection in HIV acquisition, including determining the one-year incidence of HIV among high-risk MSM in India;and collecting data on the prevalence and incidence of anogenital HPV infection, HPV-associated disease and associated risk factors in this population.